PKA, PKC, and AKAP localization in and around the neuromuscular junction

Guy A. Perkins, Lin Wang, Lily Jun Shen Huang, Kenneth Humphries, Virginia J. Yao, Maryann Martone, Thomas J. Deerinck, David M. Barraclough, Jonathan D. Violin, Donelson Smith, Alexandra Newton, John D. Scott, Susan S. Taylor, Mark H. Ellisman

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Background: One mechanism that directs the action of the second messengers, cAMP and diacylglycerol, is the compartmentalization of protein kinase A (PKA) and protein kinase C (PKC). A-kinase anchoring proteins (AKAPs) can recruit both enzymes to specific subcellular locations via interactions with the various isoforms of each family of kinases. We found previously that a new class of AKAPs, dual-specific AKAPs, denoted D-AKAP1 and D-AKAP2, bind to RIα in addition to the RII subunits. Results: Immunohistochemistry and confocal microscopy were used here to determine that D-AKAP1 colocalizes with RIα at the postsynaptic membrane of the vertebrate neuromuscular junction (NMJ) and the adjacent muscle, but not in the presynaptic region. The labeling pattern for RIα and D-AKAP1 overlapped with mitochondrial staining in the muscle fibers, consistent with our previous work showing D-AKAP1 association with mitochondria in cultured cells. The immunoreactivity of D-AKAP2 was distinct from that of D-AKAP1. We also report here that even though the PKA type II subunits (RIIα and RIIβ) are localized at the NMJ, their patterns are distinctive and differ from the other R and D-AKAP patterns examined. PKCβ appeared to colocalize with the AKAP, gravin, at the postsynaptic membrane. Conclusions: The kinases and AKAPs investigated have distinct patterns of colocalization, which suggest a complex arrangement of signaling micro-environments. Because the labeling patterns for RIα and D-AKAP 1 are similar in the muscle fibers and at the postsynaptic membrane, it may be that this AKAP anchors RIa in these regions. Likewise, gravin may be an anchor of PKCβ at the NMJ.

Original languageEnglish (US)
Article number17
JournalBMC Neuroscience
Volume2
DOIs
StatePublished - Oct 23 2001

ASJC Scopus subject areas

  • Neuroscience(all)
  • Cellular and Molecular Neuroscience

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